Editing Α-Ketoglutaric acid (section)

====Aging and diseases associated with aging====
α-Ketoglutarate has been reported to increase the [[maximum life span|life span]] and/or delay the development of old age-related diseases in a [[species]] of [[roundworm]]s and in mice. It nearly doubled the life span and delayed age-related deteriorations (e.g., decline in rapid, coordinated body movements) of ''[[Caenorhabditis elegans]]'' roundworms when added to their [[cell cultures]].<ref name="pmid26759695"/><ref name="pmid24828042">{{cite journal | vauthors = Chin RM, Fu X, Pai MY, Vergnes L, Hwang H, Deng G, Diep S, Lomenick B, Meli VS, Monsalve GC, Hu E, Whelan SA, Wang JX, Jung G, Solis GM, Fazlollahi F, Kaweeteerawat C, Quach A, Nili M, Krall AS, Godwin HA, Chang HR, Faull KF, Guo F, Jiang M, Trauger SA, Saghatelian A, Braas D, Christofk HR, Clarke CF, Teitell MA, Petrascheck M, Reue K, Jung ME, Frand AR, Huang J | title = The metabolite α-ketoglutarate extends lifespan by inhibiting ATP synthase and TOR | journal = Nature | volume = 510 | issue = 7505 | pages = 397–401 | date = June 2014 | pmid = 24828042 | pmc = 4263271 | doi = 10.1038/nature13264 | url = }}</ref> Similarly, mice fed a diet high in calcium-bound α-ketoglutarate had a longer life span and shorter length of time in which they suffered old age-related morbidities (e.g., increased frailty, hair loss, and changes in body weight). Cell cultures of [[splenocyte]]s (i.e., primarily [[T cells]]) from the α-ketoglutarate-fed mice produced higher levels of the anti-inflammatory [[cytokine]], [[interleukin-10]], than splenocytes from mice not fed α-ketoglutarate.<ref name="pmid32877690"/><ref name="pmid34952764"/> (Chronic low-grade inflammation which might be inhibited by interleukin-10, is associated with the development of old age-related disorders and diseases.<ref name="pmid36637079">{{cite journal | vauthors = Islam MT, Tuday E, Allen S, Kim J, Trott DW, Holland WL, Donato AJ, Lesniewski LA | title = Senolytic drugs, dasatinib and quercetin, attenuate adipose tissue inflammation, and ameliorate metabolic function in old age | journal = Aging Cell | volume = 22 | issue = 2 | pages = e13767 | date = February 2023 | pmid = 36637079 | pmc = 9924942 | doi = 10.1111/acel.13767 | url = }}</ref>)

As individuals age, their [[DNA]] develops additions of a [[methyl group]] (-{{chem2|CH3}}) to a [[cystine]] adjacent to a [[guanine]] (termed a [[CpG site#CgP island|CpG island]]) in an increasing number of CpG islands close to certain genes. These [[methylation]]s often suppress the [[Gene expression|expression]] of the genes to which they are close. Assays (termed [[epigenetic clock]] tests) that determine the presence of methylations of cystines in CpG islands for genes have been used to define an individual's biological age.<ref name="pmid35968782">{{cite journal | vauthors = Soto-Palma C, Niedernhofer LJ, Faulk CD, Dong X | title = Epigenetics, DNA damage, and aging | journal = The Journal of Clinical Investigation | volume = 132 | issue = 16 | pages = | date = August 2022 | pmid = 35968782 | pmc = 9374376 | doi = 10.1172/JCI158446 | url = }}</ref><ref name="pmid36304336">{{cite journal | vauthors = Chen L, Ganz PA, Sehl ME | title = DNA Methylation, Aging, and Cancer Risk: A Mini-Review | journal = Frontiers in Bioinformatics | volume = 2 | issue = | pages = 847629 | date = 2022 | pmid = 36304336 | pmc = 9580889 | doi = 10.3389/fbinf.2022.847629 | doi-access = free | url = }}</ref><ref name="pmid37657418">{{cite journal | vauthors = Moqri M, Herzog C, Poganik JR, Justice J, Belsky DW, Higgins-Chen A, Moskalev A, Fuellen G, Cohen AA, Bautmans I, Widschwendter M, Ding J, Fleming A, Mannick J, Han JJ, Zhavoronkov A, Barzilai N, Kaeberlein M, Cummings S, Kennedy BK, Ferrucci L, Horvath S, Verdin E, Maier AB, Snyder MP, Sebastiano V, Gladyshev VN | title = Biomarkers of aging for the identification and evaluation of longevity interventions | journal = Cell | volume = 186 | issue = 18 | pages = 3758–3775 | date = August 2023 | pmid = 37657418 | pmc = 11088934 | doi = 10.1016/j.cell.2023.08.003 | url = }}</ref> The Rejuvant® study reported that the median and range of the biological age of females before treatment was 62.15 (range, 46.4 to 73) years and fell to 55.55 (range 33.4 to 63.7) years after an average of 7 months treatment. These values for men were 61.85 (range 41.9 to 79.7) years before and 53.3 (33 to 74.9) years after treatment.<ref name="pmid34952764"/><ref name="pmid34847066">{{cite journal | vauthors = Demidenko O, Barardo D, Budovskii V, Finnemore R, Palmer FR, Kennedy BK, Budovskaya YV | title = Rejuvant®, a potential life-extending compound formulation with alpha-ketoglutarate and vitamins, conferred an average 8 year reduction in biological aging, after an average of 7 months of use, in the TruAge DNA methylation test | journal = Aging | volume = 13 | issue = 22 | pages = 24485–24499 | date = November 2021 | pmid = 34847066 | pmc = 8660611 | doi = 10.18632/aging.203736 | url = }}</ref> Overall, the combined group of males and females showed an average fall in biological age of 8 years compared to before treatment. The ''p''-value for this difference was extraordinarily significant, i.e., 6.538x10-12, in showing that this treatment decreased the participants' biological ages. However, the study did not: '''a)''' include a [[Placebo-controlled study|control group]] (i.e., concurrent study of individuals taking a [[placebo]] instead of Rejuvant®); '''b)''' determine if the retinyl palmitate, vitamin A, and/or calcium given with α-ketoglutarate contributed to the changes in biological ages; and '''c)''' disclose which genes were tracked for the methylation of their CpG island. The study recommended that studies need to include control groups taking a placebo or the appropriate dosages of retinyl palmitate, vitamin A, and calcium. Also, TruMe Labs, who were the maker and marketer of the biological age assay used in this study, sponsored part of the study and contributed three of its employees as authors to the study.<ref name="pmid34847066"/>